The major emphasis of this proposal is to study the proliferation and function of mononuclear phagocytes that appear in large numbers at the site of an acute inflammatory reaction. Mononuclear phagocyte colony forming cells (CFC) are identified by their ability to form colonies on the surface of glass or plastics. They appear to be a class of mononuclear phagocytes since they have very strong phagocytic activity and are adherent cells. The kinetics of macrophage proliferation from various sources will be studied in detail to determine the precursor cells' proliferative capacity, their cell cycle parameters and growth fraction. Furthermore, studies are planned to identify variables within the culture system which influence their proliferative capacity. These studies are important so that greater numbers of progeny can be obtained for functional studies. We also plan to determine whether heterogeneity of function is associated with distinct subpopulations or whether every macrophage, regardless of source, can express every function. Local environment factors which influence macrophage function will also be investigated. Initial functional studies will emphasize their role in interferon production, viral replication, elastase production, plasminogen activator production, collagenase production and tumoricidal activity. The role of macrophage growth factor in the regulation of macrophage proliferation will also be studied in detail. Since we have been able to culture a single CFC in microtiter wells which yield an average of 25,000 progeny in 30 days, the functional heterogeneity of these cells will be explicitly defined. Various sources besides the peritoneal exudate macrophage will also be tested to determine whether proliferative capability and function differ. Since the mononuclear phagocyte system plays an important role in defense against both tumors and microorganisms, the results of these studies will be useful in understanding and improving the host defense mechanisms.